Single domain and multidomain derivatized magnetic particles have been used for ligand-receptor binding measurements in a technique called “MAgnetic Relaxation ImmunoAssay” (MARIA). Ligand-receptor binding determination using MARIA has been described by Eberbeck, D. et al. J. Magnet. Magn. Mat., 2005, 289:435-38; Haller, A. et al. IEEE Transactions on Applied Superconductivity, 2001, 11:1371-74; Ludwig, F. et al. J. Magnet. Magn. Mat., 2005 293:690-95; Matz, H. Applied Superconductivity, 1999, 6:577-83; Kötitz, R. J. App. Phys., 1997, 81:4317; Kotitz, R. et al. J. of Magnet. Magn. Mat., 1999, 194:62-68; Weitschies, W. Pharm. Pharmacol. Lett., 1997, 7:1-7; Chemla, Y. et al. PNAS, 2000, 97:14268-72.
MARIA involves suspending ligand-derivatized particles in solvated receptors, applying a momentary strong magnetic field to align and magnetize the particles, and then turning off the field and measuring the remnant sample magnetization with a SQUID. Non-binding particles will rapidly randomize their orientations due to Brownian motion, resulting in a rapid decay of the SQUID signal. Binding particles will rotate slower due to frictional and momentum effects, causing the SQUID signal to decay more slowly. This technique can be used in a complex biological matrix without purification steps, but only one binding experiment can be performed per sample.
Derivatized quantum dots have also been used for binding measurements (Ravindran, S. et al. Nanotechnology 2005, 1; Olivos, H. et al. Chem. BioChem. 2003, 4:1242-45). Because of the narrow emission bands, combinations of dots (i.e., multiplexing) is possible. Binding measurements have been performed using gel electrophoresis and chromatographic methods (Moini, H. et al. Methods Enzymol. 2001, 335:333-7; Hendrickson, W. BioTechniques 1985, 3:198-207; Afjehi-Sadat, L. et al. Current Proteomics 2004, 1:297-313), which exploit the differing migration speeds of the components in a mixture to effect a physical separation of the components.
Magnetic particles and quantum dots have heretofore been combined (Selvan, S. et al. Advanced Materials, in press; Yi, D. J. Am. Chem. Soc., 2005, 127:4990-91; Mulvaney, S. BioTechniques, 2004, 36:602-09) but not in an asymmetric configuration with respect to the magnetic pole, which permits novel applications to be described.